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From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior

Molecular Psychiatry volume 21, pages 491–499 (2016)Cite this article

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Abstract

Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5-CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive–compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders.

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Acknowledgements

This research was carried out within the Department of Psychology and the Department of Pharmacology of the University of Cambridge, as well as the INSERM AVENIR team Psychobiology of Compulsive Disorders of the University of Poitiers. It was supported by an INSERM AVENIR grant and a FYSSEN foundation grant to DB. M-LD was supported by a PhD fellowship from the Fondation pour la Recherche Médicale (FRM) and AB-R was supported by a post-doctoral fellowship from the INSERM. BJE was supported by the United Kingdom Medical Research Council (MRC) grant 9536855.

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Author notes

  1. A Belin-Rauscent and M-L Daniel: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, University of Cambridge, Cambridge, UK

    A Belin-Rauscent, M Puaud, D Howett, C McKenzie & D Belin

  2. Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK

    A Belin-Rauscent, M Puaud, B Jupp, S Sawiak, T W Robbins, B J Everitt, J W Dalley & D Belin

  3. Inserm CIC-1402, Université de Poitiers, Poitiers, France

    M-L Daniel

  4. Department of Psychology, University of Cambridge, Cambridge, UK

    B Jupp, T W Robbins, B J Everitt & J W Dalley

  5. Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA

    D Caprioli

  6. Neurobiologie Intégrative des Systèmes Cholinergiques, Institut Pasteur, Paris, France

    M Besson

  7. Department of Psychiatry, University of Cambridge, Cambridge, UK

    J W Dalley

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  1. A Belin-Rauscent
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  2. M-L Daniel
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  8. D Caprioli
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  9. M Besson
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Correspondence to D Belin.

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Belin-Rauscent, A., Daniel, ML., Puaud, M. et al. From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior. Mol Psychiatry 21, 491–499 (2016). https://doi.org/10.1038/mp.2015.140

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